High Relapse Rate of Acute Myeloid Leukemia with Translocation (8;21) or Inversion (16) in Elderly Patients Treated with Conventional Chemotherapy.

Abstract

Abstract Acute Myeloid Leukemias (AML) harbouring t(8;21) and Inv(16) shared a common pathogenesis with modifications in the Core Binding Factor (CBF) complex (CBF sub-units alpha and beta respectively). They also shared common clinical features with a younger age of incidence and a good prognosis related to a high efficacy of High Dose AraCytine (HDAC) chemotherapies. Nevertheless, CBF AML could also occur in elderly patients and are associated with a poorer prognosis compared to younger patients. Currently, no specific study has been focused on the reasons explaining these results. We decided to perform a monocentric retrospective analysis of the outcome of patients over 60 treated for a CBF AML with conventional chemotherapy. Both host-related and disease-related variables were integrated in the analysis. Over an observation period of 15 years, only 32 cases could be extracted from our database, representing less than 5% of the AML patients over 60y. Among them, 29 patients were treated with induction chemo. Median age was 67y (60–76) with 8 patients over 70y. Host related variables were evaluated using ECOG (2 patients with ECOG 3–4) and Sorror’s Hematopoietic Stem Cell Transplantation Comorbidity Index (7 patients with HCT-CI =2 or higher). Secondary AML represented 10 cases (8 with Inv(16)). Cytogenetics showed 22 Inv(16) and 7 t(8;21). Additional cytogenetic abnormalities were found in 9 patients (50% of t(8;21) cases) and kit mutation in 20% of the cases. High WBC count (over 30G/l) was found in 12 cases (10 with Inv(16)) and CNS involvement in 3 cases. Induction therapy used Idarubicin 8mg/m2 3 days and cytarabine 100mg/m2/24h 7 days in most of the patients. Induction mortality was 10% and 8 patients needed to be admitted in ICU (4 with High ECOG or HCT-CI). Second Induction was performed for 3 patients and global Complete Remission rate was 90%. Post induction therapy used at least one consolidation chemo (Ida + Ara-C) followed by HDAC (11 cases), maintenance chemo (9 cases), autologous Stem Cell Transplantation (SCT) (4 cases), or allogeneic SCT (1 case). Intensive consolidation with one or more HDAC or SCT was not associated with significant toxicity. Molecular response was evaluated during consolidation for 11 patients and all but one achieved a major response. With a median follow-up of 15 months, 3-year probability of Overall Survival and Relapse Free Survival were respectively 36% and 18%. There is a trend to a better RFS for patients without high WBC count (p=0.09) but neither age, HCT-CI, cytogenetics, use of Intensive consolidation or molecular response were significantly associated with OS or RFS. These results suggest that conventional induction therapy should be systematically considered for CBF AML with acceptable toxicities and high CR rate. Nevertheless, virtually all the patients relapsed quickly during post remission therapy even if intensive chemotherapy was administrated. Considering the recent advances in our knowledge of the pathogenesis of CBF AML, the use of monoclonal antibodies (Gemtuzumab), tyrosine kinase inhibitors, epigenetic agents or reduced intensity allogeneic SCT should be further evaluated in this situation.